Select Topic:
Browse by Series:

Molecular Testing for Stage III Melanoma

Panelists: Axel Hauschild, MD, University Hospital Schleswig-Holstein; Michael A. Davies, MD, PhD UT MD Anderson Cancer Center; Jason J. Luke, MD, FACP, University of Chicago; Caroline Robert, MD, PhD Gustave-Roussy; Merrick I. Ross, MD UT MD Anderson Cancer Center
Published: Thursday, Dec 06, 2018



Transcript: 

Michael A. Davies, MD, PhD: So there is a consensus to estimate the volume of the micrometastasis in the sentinel node. This is done routinely. Caroline, what else needs to be reported if we are talking about micrometastasis from sentinel nodes? Are you doing any reporting on molecular status, let’s say for BRAF-mutation status? Are you doing some evaluation on tumor mutational burden and things like this? Are there any biomarkers that need to be reported by the pathologist?

Caroline Robert, MD, PhD: For the clinic, we do BRAF-mutation testing for primary melanoma and stage III disease.

Axel Hauschild, MD: If you have a tiny micrometastasis that is 1 mm, how are you doing the BRAF testing? Or are you going back to the primary tumor?

Caroline Robert, MD, PhD: We do both, and we also do immunostaining. If you have very few cells, this is a situation where you might miss it by the molecular biology but see that it is a V600E mutation, which is good and is well standardized. So we definitely search for BRAF mutations. All the other things—tumor mutation burden, or CD8, or programmed death-ligand 1 (PD-L1)—we do only in the research field. This information is not being used to take care of patients.

Merrick I. Ross, MD: Caroline, with immunostaining you can’t detect V600K, right?

Caroline Robert, MD, PhD: No.

Merrick I. Ross, MD: It’s useful only for V600?

Caroline Robert, MD, PhD: Absolutely. In think in the future, probably like in breast cancer, there will be a lot of immunostaining. For the negative patients, we will go to the molecular biology for BRAF. It’s not problematic. It’s not like PD-L1 staining, for example, and V600E mutations.

Jason J. Luke, MD, FACP: Can I make a comment on that? I want to reinforce something that you mentioned because this is something that has really started coming up a lot in clinical practice. It really ought to be the case that it’s reflexive testing. If a node is positive in a pathology department, they should send for BRAF—whether it’s an antibody test or a molecular test. The reason that I say that is because when patients eventually come to see us, if we don’t have that information, we cannot have the conversation. We can, in general, speak about it, but it becomes difficult to decide on therapy. You have multiple therapies you can consider, and they have different pros and cons, but you don’t know whether or not one of them is reasonable. I can’t emphasize that enough. That’s a test that needs to be done right away so that subsequent decision-making can take place.

Caroline Robert, MD, PhD: And if we don’t have that information we should go back to the primary, because it’s very rare that it’s not consistent.

Axel Hauschild, MD: Mike, you are known as a biomarker expert. Are you looking for any other markers on routine scans, like PD-L1 testing? I think this is a hot topic to discuss for metastatic melanoma, but in the adjuvant setting, it might be even hotter. What’s your opinion?

Michael A. Davies, MD, PhD: No, at this point there’s a clear indication for doing BRAF testing. Again, I agree with Caroline. The immunohistochemistry test is very sensitive. If it’s negative, you do need to do the full DNA-based testing. At this point, we do not utilize PD-L1 testing in stage III patients to guide our management at all. We really are not doing that testing in the clinical setting. There is a lot of research interest on whether this will affect our management in future years. At this point, it is not a standard test that we’re doing clinically.

Merrick I. Ross, MD: Yes, I agree with that. It’s really a research tool at the present time. If you look at the data from the adjuvant trials for immunotherapy, PD-L1 expression didn’t really seem to have an impact on the efficacy of these drugs.

Axel Hauschild, MD: It’s true.

Transcript Edited for Clarity 

SELECTED
LANGUAGE
Slider Left
Slider Right


Transcript: 

Michael A. Davies, MD, PhD: So there is a consensus to estimate the volume of the micrometastasis in the sentinel node. This is done routinely. Caroline, what else needs to be reported if we are talking about micrometastasis from sentinel nodes? Are you doing any reporting on molecular status, let’s say for BRAF-mutation status? Are you doing some evaluation on tumor mutational burden and things like this? Are there any biomarkers that need to be reported by the pathologist?

Caroline Robert, MD, PhD: For the clinic, we do BRAF-mutation testing for primary melanoma and stage III disease.

Axel Hauschild, MD: If you have a tiny micrometastasis that is 1 mm, how are you doing the BRAF testing? Or are you going back to the primary tumor?

Caroline Robert, MD, PhD: We do both, and we also do immunostaining. If you have very few cells, this is a situation where you might miss it by the molecular biology but see that it is a V600E mutation, which is good and is well standardized. So we definitely search for BRAF mutations. All the other things—tumor mutation burden, or CD8, or programmed death-ligand 1 (PD-L1)—we do only in the research field. This information is not being used to take care of patients.

Merrick I. Ross, MD: Caroline, with immunostaining you can’t detect V600K, right?

Caroline Robert, MD, PhD: No.

Merrick I. Ross, MD: It’s useful only for V600?

Caroline Robert, MD, PhD: Absolutely. In think in the future, probably like in breast cancer, there will be a lot of immunostaining. For the negative patients, we will go to the molecular biology for BRAF. It’s not problematic. It’s not like PD-L1 staining, for example, and V600E mutations.

Jason J. Luke, MD, FACP: Can I make a comment on that? I want to reinforce something that you mentioned because this is something that has really started coming up a lot in clinical practice. It really ought to be the case that it’s reflexive testing. If a node is positive in a pathology department, they should send for BRAF—whether it’s an antibody test or a molecular test. The reason that I say that is because when patients eventually come to see us, if we don’t have that information, we cannot have the conversation. We can, in general, speak about it, but it becomes difficult to decide on therapy. You have multiple therapies you can consider, and they have different pros and cons, but you don’t know whether or not one of them is reasonable. I can’t emphasize that enough. That’s a test that needs to be done right away so that subsequent decision-making can take place.

Caroline Robert, MD, PhD: And if we don’t have that information we should go back to the primary, because it’s very rare that it’s not consistent.

Axel Hauschild, MD: Mike, you are known as a biomarker expert. Are you looking for any other markers on routine scans, like PD-L1 testing? I think this is a hot topic to discuss for metastatic melanoma, but in the adjuvant setting, it might be even hotter. What’s your opinion?

Michael A. Davies, MD, PhD: No, at this point there’s a clear indication for doing BRAF testing. Again, I agree with Caroline. The immunohistochemistry test is very sensitive. If it’s negative, you do need to do the full DNA-based testing. At this point, we do not utilize PD-L1 testing in stage III patients to guide our management at all. We really are not doing that testing in the clinical setting. There is a lot of research interest on whether this will affect our management in future years. At this point, it is not a standard test that we’re doing clinically.

Merrick I. Ross, MD: Yes, I agree with that. It’s really a research tool at the present time. If you look at the data from the adjuvant trials for immunotherapy, PD-L1 expression didn’t really seem to have an impact on the efficacy of these drugs.

Axel Hauschild, MD: It’s true.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Evolving Roles for Targeted Melanoma Therapies: Assessing Rapid Progress in the Field and Looking Toward Future CombinationsFeb 28, 20191.5
Advances in™ Melanoma: Exploring BRAF/MEK in Adjuvant and Neoadjuvant SettingsSep 28, 20191.5
Publication Bottom Border
Border Publication
x